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Updated: Jun 25, 2026

Quantitation of Endothelial Cell Adhesiveness In Vitro
Published on: June 18, 2015
Effects of statins on adhesion molecule expression in endothelial cells
Y Dimitrova1, S Dunoyer-Geindre, G Reber
1Division of Angiology and Haemostasis, University Hospital of Geneva, Geneva, Switzerland.
Insights
Statins like simvastatin may increase the expression of adhesion molecules on endothelial cells, potentially contributing to atherosclerosis. This effect appears linked to the inhibition of geranylgeranylated proteins.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pharmacology
Background:
- HMG-CoA reductase inhibitors (statins) are crucial for preventing atherosclerosis.
- Adhesion molecule expression on activated endothelial cells (EC) drives atherosclerosis initiation and progression.
Purpose of the Study:
- To investigate the impact of simvastatin, fluvastatin, and pravastatin on adhesion molecule expression in activated EC.
- To elucidate the underlying mechanisms of statin-induced effects on EC activation.
Main Methods:
- Human EC were pretreated with statins, with or without mevalonate or isoprenoid intermediates (FPP, GGPP).
- EC were activated with TNF-alpha or LPS, and adhesion molecule expression (E-selectin, VCAM-1) was measured.
- Experiments included selective inhibitors of geranylgeranyltransferase (GGTI-286) and farnesyltransferase (FTI-277).
Main Results:
- Statins potentiated TNF-alpha and LPS-induced E-selectin and VCAM-1 expression.
- Mevalonate and GGPP reversed the statin-induced potentiation; FPP showed a partial effect.
- GGTI-286 mimicked statin effects, increasing E-selectin expression, unlike FTI-277.
Conclusions:
- Statins enhance E-selectin and VCAM-1 expression in TNF-alpha/LPS-stimulated EC.
- Inhibition of geranylgeranylated proteins may mediate statin-induced changes in EC adhesion molecule expression.
Background:
Inhibitors of HMG-CoA reductase are widely used to prevent atherosclerosis progression. The expression of adhesion molecules on activated endothelial cells (EC) is an important step in the initiation and progression of atherosclerosis.
Objectives:
We investigated whether adhesion molecule expression on activated EC is influenced by simvastatin, fluvastatin and pravastatin and, if so, by which mechanisms.
Methods:
Human EC from umbilical veins or saphenous veins were pretreated overnight with statins with or without mevalonate, and also for simvastatin or fluvastatin with the isoprenoid intermediates, farnesyl pyrophosphate (FPP), or geranylgeranyl pyrophosphate (GGPP). After 4-6 h activation with tumor necrosis factor (TNF)-alpha or lipopolysaccharide (LPS), surface adhesion molecule expression was evaluated by ELISA and by flow cytometry. The same experiments were performed with selective inhibitors of geranylgeranyltransferase (GGTI-286) and farnesyltransferase (FTI-277).
Results:
Pretreatment with simvastatin, fluvastatin or pravastatin potentiated the TNF-alpha and LPS-induced expression of E-selectin and VCAM-1, and mevalonate reversed the potentiating effect of these statins. GGPP also reversed the potentiating effect of simvastatin or fluvastatin on adhesion molecule expression, while FPP only partially reversed this effect. Furthermore, GGTI-286, but not FTI-277, mimicked the effect of simvastatin by increasing the TNF-alpha-mediated overexpression of E-selectin.
Conclusions:
Statins increase E-selectin- and VCAM-1-induced expression on vascular endothelial cells stimulated with TNF-alpha or LPS. The inhibition of geranylgeranylated proteins could contribute to this effect.
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